The long range objectives of this program are to contribute to the definition of the structure, regulation, evolution, and biological function of genes which have known or suspected key roles in neurobiological processes. The focus of attention is currently on the dunce gene of Drosophila melanogaster, the first of a set of genes identified whose normal function is required for learning and/or memory. Flies carrying lesions within the dunce gene learn normally, but exhibit an ephemeral memory. Indirect evidence suggests that dunce codes for cAMP phosphodiesterase, an enzyme which degrades the small molecule cycle AMP. A direct demonstration of this may be possible by determining if the enzyme is produced, when dunce+ sequence information is added to and expressed in another cell type, such as amphibian oocytes or bacteria. Structural studies of the isolated gene, including DNA sequencing, will define its architecture, as well as provide the amino acid sequence of the polypeptide product. Transformation of dunce mutants with dunce+ sequences will be initiated to examine the regulation and biological function of the gene. A phylogenetic survey for "dunce+" sequences across class and phyla boundaries will be conducted to determine the extent of evolutionary conservation of dunce+, and to establish a basis for studying the structure and biological function of these sequences in other organisms, such as the mouse. These studies will provide a detailed picture of this gene whose function is necessary for memory, and will furnish a foundation for studying other genes which function in higher animal behavior.